4-Chlorophenol → 2-(4-Chlorophenoxy)-4-methyl-1-nitrobenzene

HRID 1642259Notes

Reaction equation

HRID 1642259 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.F[C:10]1[CH:11]=[C:12]([CH3:19])[CH:13]=[CH:14][C:15]=1[N+:16]([O-:18])=[O:17].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.[OH-].[Na+]>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:10]2[CH:11]=[C:12]([CH3:19])[CH:13]=[CH:14][C:15]=2[N+:16]([O-:18])=[O:17])=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 46844-ChlorophenolHCID 11430Potassium CarbonateHCID 67966Benzene, 2-fluoro-4-methyl-1-nitro-

Product 1

HCID 667553372-(4-Chlorophenoxy)-4-methyl-1-nitrobenzeneYield 105.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 14798Sodium HydroxideSolvent

Procedure

A solution of 4-chlorophenol (1 g, 7.78 mmol), 3-fluoro-4-nitrotoluene (808 mg, 5.21 mmol) and potassium carbonate (1.29 g, 9.34 mmol) in DMF (5 ml) was stirred at reflux for 6 h. The reaction mixture was allowed to cool and then re-dissolved in 2.5M NaOH (10 ml). This aqueous mixture was then extracted with ethyl acetate (3×15 ml) and the combined organics were dried (MgSO4), filtered and concentrated in vacuo. An ethyl acetate solution of the crude material was filtered through a pad of silica which upon evaporation in vacuo afforded 2-(4-chlorophenoxy)-4-methyl-1-nitrobenzene as a yellow oil (1.45 g). This oil was then dissolved in 10:1 EtOH:H2O (10 ml) and added to a refluxing solution of iron powder (1.20 g, 21.53 mmol) and ammonium chloride (147 mg, 2.74 mmol) in 10:1 EtOH:H2O (20 ml). Stirring at this temperature continued for a further 2 h, before the reaction mixture was allowed to cool. The mixture was then filtered through a pad of celite, which was further washed with ethyl acetate (250 ml). Concentration in vacuo followed by purification by flash chromatography (eluant: 8:2 to 1:1 hexane:ethyl acetate) afforded the title compound as a pale yellow solid (868.2 mg, 70%). 1H NMR (270 MHz, CDCl3): δ 2.20 (3H, s, CH3), 3.65 (2H, br s, NH2), 6.65-6.68 (1H, m, Ar—H), 6.72 (1H, d, J=10.9 Hz, Ar—H), 6.78-6.82 (1H, m, Ar—H), 6.85-6.91 (2H, m, Ar—H), 7.21-7.26 ppm (2H, m, Ar—H).

Workup

  1. temperatureat reflux for 6 h
  2. temperatureto cool
  3. extractionThis aqueous mixture was then extracted with ethyl acetate (3×15 ml)
  4. dry with materialthe combined organics were dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. filtrationAn ethyl acetate solution of the crude material was filtered through a pad of silica which upon evaporation in vacuo

Sources & evidence

ORD record
ord-5f201239042a449382821d3a1c1015d9
Source dataset
uspto-grants-2012_02
Patent number
US08119627B2

Reaction notes

Loading…